rs1142326

chr6-32641435-C-Achr6-32641435-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_002122.5(HLA-DQA1):c.208C>A(p.Arg70=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 13)
  • Exomes 𝑓: 0.0034 (393 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

Genes affected

HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.255 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 151 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQA1	NM_002122.5	c.208C>A	p.Arg70=	synonymous_variant	2/5	ENST00000343139.11
HLA-DQA1	XM_006715079.5	c.208C>A	p.Arg70=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.208C>A	p.Arg70=	synonymous_variant	2/5		NM_002122.5	P1

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 114 AN: 77196 Hom.: 1 Cov.: 13

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00129

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.000780

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.000690

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00170

Gnomad OTH AF: 0.00211

GnomAD3 exomes AF: 0.0107 AC: 1799 AN: 167538 Hom.: 151 AF XY: 0.0110 AC XY: 1006 AN XY: 91660

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.00709

Gnomad ASJ exome AF: 0.0127

Gnomad EAS exome AF: 0.00509

Gnomad SAS exome AF: 0.00965

Gnomad FIN exome AF: 0.00393

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.00823

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00342 AC: 3154 AN: 923200 Hom.: 393 Cov.: 27 AF XY: 0.00400 AC XY: 1857 AN XY: 464830

Gnomad4 AFR exome AF: 0.00317

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00818

Gnomad4 EAS exome AF: 0.00174

Gnomad4 SAS exome AF: 0.00829

Gnomad4 FIN exome AF: 0.00186

Gnomad4 NFE exome AF: 0.00279

Gnomad4 OTH exome AF: 0.00337

GnomAD4 genome AF: 0.00148 AC: 114 AN: 77282 Hom.: 1 Cov.: 13 AF XY: 0.00157 AC XY: 59 AN XY: 37594

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00129

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.000784

Gnomad4 SAS AF: 0.00168

Gnomad4 FIN AF: 0.000690

Gnomad4 NFE AF: 0.00170

Gnomad4 OTH AF: 0.00206

Alfa AF: 0.0238 Hom.: 319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	2.1
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1142326; hg19: chr6-32609212; COSMIC: COSV58237183; COSMIC: COSV58237183;